August 31, 2010 - A large new study confirmed the benefits of HAS Prophylactic mastectomy and salpingo-oophorectomy in women with BRCA1 and BRCA2 Mutations. Women who went under the Prophylactic surgery had a greatly reduced risk for breast or ovarian cancer and a reduction in cancer-related mortality.

The Findings Appear in the September 1 issue of JAMA.

This study adds evidence supporting the benefits of preventive surgery - that it can-reducing the risk for cancer-related mortality and for breast / ovarian cancer Developing in the first place, Explained senior author Timothy Rebbeck, PhD, professor of epidemiology at the University of Pennsylvania School of Medicine in Philadelphia.

Dr. Rebbeck and Colleagues Investigated a cohort of nearly 2500 women with BRCA1 or BRCA2 Mutations, 10% chose to undergo a Whom risk-reducing mastectomy and 38% of Whom chose a risk-reducing salpingo-oophorectomy.

No breast cancer were diagnosed in the women who went under the constantly mastectomy 3 years or prospective follow-up. However, 7% did not undergo, or Those Who Prophylactic mastectomy a consistently a similar follow-up period were diagnosed with breast cancer.

There were no cases of ovarian cancer events consistently the six years or prospective follow-up in BRCA2 carriers without previous breast cancer who under went salpingo-oophorectomy. Conversely, 3% or women who did not undergo the procedure on a similar follow-up period were diagnosed with the disease.

Among BRCA1 carriers with a previous diagnosis of breast cancer, a salpingo-oophorectomy going under was associated with a reduced risk for ovarian cancer (hazard ratio [HR], 0.15, 95% confidence interval [CI], 0.04 - 0.63), there were no cases diagnosed in BRCA2 carriers.

Overall, results showed That, compared with women who did not undergo Prophylactic salpingo-oophorectomy, Those who under went the procedure had an overall lower risk for ovarian cancer, Including Those with previous breast cancer (6% vs. 1%, HR 0.14, 95 % CI, 0.04 - 0.59) and Those without previous breast cancer (6% vs 2%, HR 0.28, 95% CI, 0.12 - 0.6), lower risk for a first diagnosis of breast cancer in BRCA1 carriers (20% vs 14 %, HR 0.63, 95% CI, 0.41 - 0.96) and BRCA2 carriers (23% vs 7%, HR 0.36, 95% CI, 0.16 - 0.82), lower all-cause mortality (10% vs 3%; HR , 0.40, 95% CI, 0.26 - 0.61), lower breast-cancer-specific mortality (6% vs 2%, HR 0.44, 95% CI, 0.26 - 0.76), and lower ovarian-cancer-specific mortality (3% vs. 0.4%, HR 0.21, 95% CI, 0.06 - 0.80).

Data for Surveillance Group Limited

The women who opted not to have surgery Prophylactic were counseled to undergo intensive screening. Although surveillance Is not prevention, it can result in detection and improved survival EARLIER, but the nonsurgery group of the study was not specifically Evaluated for surveillance practices, said Dr.. Rebbeck.

"We do not have data on the survival or mortality in women who went under optimal screening," he told Medscape Medical News. "Having said That, the breast cancer risk reduction among women in the oophorectomy group but is Substantial Comparable to That in the general population of women who fuel tamoxifen."

There are no data to date for women with BRCA1 / 2 Mutations and primary prevention of breast cancer with tamoxifen use, he added. "While there are no comparison data available, it May Be Possible thats the risk reduction by oophorectomy is Comparable to That of Other Measures."

But Dr. Rebbeck emphasized an important point to remember That Is That Primarily oophorectomy is recommended to reducing ovarian cancer risk or death, not breast cancer. "Women Should Be Using oophorectomy as an ovarian cancer prevention tool - the benefit to breast cancer is just a side benefit," he said.

Importance of Counseling, Genetic Testing Fear of

It is important to identify and counsel women who have a family history of breast cancer, so That They Will better understand risks and Their options, and ways to reducing Those risks, the authors note, or an Accompanying editorial.

"At a minimum, primary care clinicians Should Be familiar with the American Society of Clinical Oncology or National Comprehensive Cancer Network guidelines and Should Be Able to refer at-risk patients to a genetic counselor," write Laura Esserman, MD, MBA, from University of California, San Francisco, and Virginia Kaklamani, MD, DSc, from Northwestern University, Chicago, Illinois.

The editorialists point out there are better Now That That data available on the potential outcomes of interventions thesis, women can make more informed choices about whether to opt for Prophylactic surgery or intensive surveillance.

But eventhough the techniques for Prophylactic surgery and cosmetic options have improved, many women still might not opting for this. In Such cases, there are other approaches are less invasive than surgery That but more aggressive than surveillance, Dr. Explained. Kaklamani.

"We have chemo preventive agent tamoxifen Such As That can help, and there are other agents are being tested That, Such As PARP inhibitors," she told Medscape Medical News.

In Addition, some people fear the Implications That positive genetic testing for BRCA Mutations Including Those, can have on Their insurance premiums. The Genetic Information Nondiscrimination Act of 2008 was designed to protect people from insurance and Employer Discrimination on the basis of genetic tests, and Dr.. The Importance of Kaklamani emphasized educating women about this.

"There are laws protect us from That Discrimination from genetic testing and insurance, with this study, we now Know That That We recommend procedures have a positive impact on survival," she said.

Evidence Added

The study adds to the growing body of literature Concerning the Benefits of Prophylactic surgery for women with BRCA1 / 2 Mutations. Axis Previously reported by Medscape Medical News, 4 separate analysis showed bilateral That having a mastectomy reduced the risk for breast cancer by 90%.

Another study found women carrying the BRCA gene That mutation who under went a Prophylactic mastectomy for breast cancer risk Their reduced to less than 1%. Although estimates Vary, mutation carriers have an Approximate lifetime risk for breast cancer ranges from 56% to That 84%.

Improved Mechanisms Research Needed

"The discovery of biomarkers That Individuals identify high-risk for a specific disease biomarkers and integration thesis or enter clinical practice Enables the systematic study or thesis populations - and development and testing of interventions to reducing Their risk," write the editorialists.

They note thats the study required more than 20 clinical Collaborating Centres to collect data from women who participated Thousands of in the research, and point out better methods are needed That.

Improved Mechanisms are needed to study and Evaluate "the introduction of new tests like BRCA gene mutation testing, and to capture the key pieces of information-identified - Such As the uptake of testing, results, clinical Decisions, and Outcomes - That so clinicians and researchers can continually learn from Their Experience, "they write.

The study was supported by grants and funding from the Public Health Service, the University of Pennsylvania Cancer Center, the Cancer Genetics Network, the Research Fund Marjorie Cohen, SPORE grant from the Dana-Farber/Harvard Cancer Center, the U.S. Department of Defense, the Utah Cancer Registry and the Utah State Department of Health, Nebraska State Cancer and Smoking-Related Diseases Research Program, Cancer Research UK, National Cancer Institute and the National Institute for Health Research. Olufunmilayo I. Olopade, MD, a Coauthor of the study from the University of Chicago Medical Center in Illinois, reports Receiving funding as the Doris Duke Distinguished Clinical Scientist. The study authors and editorialists have disclosed no relevant financial relationships.

JAMA. 2010, 304:967-975, 1011-1012.